A new method of wound treatment: targeted therapy of skin wounds with reactive oxygen species-responsive nanoparticles containing SDF-1α

Tao Tang,1,* Hao Jiang,1,* Yuan Yu,2,* Fang He,1 Shi-zhao Ji,1 Ying-ying Liu,1 Zhong-shan Wang,1 Shi-chu Xiao,1 Cui Tang,3 Guang-Yi Wang,1 Zhao-Fan Xia1 1Department of Burn Surgery, The Second Military Medical University Affiliated Changhai Hospital, 2Department of Pharmaceutics, School of Pharmacy, The Second Military Medical University, 3State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai, People’sRepublic of China *These authors contributed equally tothis work Objective: To accelerate wound healing through promoting vascularization by using reactive oxygen species (ROS)-responsive nanoparticles loaded with stromal cell-derived factor-1α (SDF-1α).Methods: The ROS-reactive nanomaterial poly-(1,4-phenyleneacetone dimethylene thioketal) was synthesized, and its physical and chemical properties were characterized. ROS-responsive nanoparticles containing SDF-1α were prepared through a multiple emulsion solvent evaporation method. The loading capacity, stability, activity of the encapsulated protein, toxicity, and in vivo distribution of these nanoparticles were determined. These nanoparticles were administered by intravenous infusion to mice with full-thickness skin defects to study their effects on the directed chemotaxis of bone marrow mesenchymal stem cells, wound vascularization, and wound healing.Results: The synthesized ROS-reactive organic polymer poly-(1,4-phenyleneacetone dimethylene thioketal) possessed a molecular weight of approximately 11.5kDa with a dispersity of 1.97. ROS-responsive nanoparticles containing SDF-1α were prepared with an average diameter of 110nm and a drug loading capacity of 1.8%. The encapsulation process showed minimal effects on the activity of SDF-1α, and it could be effectively released from the nanoparticles in the presence of ROS. Encapsulated SDF-1α could exist for a long time in blood. In mice with full-thickness skin defects, SDF-1α was effectively released and targeted to the wounds, thus promoting the chemotaxis of bone marrow mesenchymal stem cells toward the wound and its periphery, inducing wound vascularization, and accelerating wound healing. Keywords: reactive oxygen species, stromal cell-derived factor-1α, bone marrow mesenchymal stem cells, wound healing